The on-going diversification of IC functionality has led to the miniaturization of many techniques, i.e. has made many techniques available on an IC. Examples of such miniaturization include (medical) laboratory techniques such as analyte analysis of bodily fluid samples and DNA sequencing techniques.
Apart from the technical challenges of the miniaturization, i.e. how to reliably reproduce detection techniques in the IC domain, a major hurdle that needs overcoming en-route to the successful commercialization of such lab-on-chip solutions is the manufacturing cost of such ICs. The manufacturing cost is in part dominated by the following two factors: process complexity and process yield. These factors are often correlated; a high manufacturing complexity, e.g. a large number of process steps, negatively affects the process yield, such that relatively complex ICs are typically costly to manufacture, as a large number of process steps is required and the yield of the process is relatively low. In addition, the manufacturing complexity significantly complicates further miniaturization of the IC, e.g. for the purpose of increasing the sensor density on the IC or for the purpose of porting the IC design to a smaller technology.
An example of a lab-on-chip device for the monitoring of DNA sequencing is disclosed in US 2010/0137143 A1. This document discloses a CMOS IC in which a plurality of pH-sensitive electrodes, i.e. pH-sensitive gate electrodes of a plurality of ChemFETs or ISFETs is located in the upper metal layer of the metallization stack of the IC. A passivation layer is formed over the metallization stack, with a plurality of silicon dioxide reaction chambers formed on the passivation stack over respective pH-sensitive gate electrodes. Each reaction chamber contains a bead to which a nucleic acid such as a sequencing primer or a self-priming nucleic acid template is covalently bound, with the FETs detecting changes in pH resulting from the release of H+-ions by the hydrolysis of the inorganic pyrophosphate released when a DNA sequence is extended.
The indirect detection of such DNA sequencing by means of monitoring pH changes is particularly promising because it allows for a more facile detection of single extensions to the DNA strand compared to direct detection methods in which capacitive changes due to such extensions are being monitored.
However, a particular drawback of the IC disclosed in US 2010/0137143 A1 is that it requires a relatively large number of additional process steps to manufacture, which adds to the cost of the IC. Also, the fact that the passivation layer is used as the pH sensitive material on the extended gate electrodes of the field effect transistors (FETs) in the metallization stack is not ideal as it limits the materials that can be used for the passivation layer to pH-sensitive materials and moreover limits the sensitivity of the FETs due to the fact that the passivation layer is required to have a minimum thickness in order to effectively protect the underlying structures of the IC from external influences.